Procoagulant Adaptation of a Blood Coagulation Prothrombinase-like Enzyme Complex in Australian Elapid Venom 英文参考文献.docVIP

Toxins 2010, 2, 1554-1567; doi:10.3390/toxins2061554 OPEN ACCESS toxins ISSN 2072-6651 /journal/toxins Review Procoagulant Adaptation of a Blood Coagulation Prothrombinase-like Enzyme Complex in Australian Elapid Venom Mettine H.A. Bos 1 and Rodney M. Camire 1,2, * 1 Department of Pediatrics, Division of Hematology, The Children’s Hospital of Philadelphia, Philadelphia, PA 19104, USA; E-Mail: bos@ 2 The University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA * Author to whom correspondence should be addressed; E-Mail: rcamire@; Tel.: +1-215-590-9968; Fax: +1-215-590-3660. Received: 30 March 2010; in revised form: 4 June 2010 / Accepted: 17 June 2010 / Published: 18 June 2010 Abstract: The macromolecular enzyme complex prothrombinase serves an indispensable role in blood coagulation as it catalyzes the conversion of prothrombin to thrombin, a key regulatory enzyme in the formation of a blood clot. Interestingly, a virtually identical enzyme complex is found in the venom of some Australian elapid snakes, which is composed of a cofactor factor Va-component and a serine protease factor Xa-like subunit. This review will provide an overview of the identification and characterization of the venom prothrombinase complex and will discuss the rationale for its powerful procoagulant nature responsible for the potent hemostatic toxicity of the elapid venom. Keywords: snake venom; blood coagulation; prothrombinase complex; factor X; factor V; prothrombin activation; serine protease; hemostatic toxin 1. Introduction Venomous snakes produce an array of toxic compounds, including procoagulant proteins, to defend themselves and incapacitate prey. Using a murine toxicity model to compare 25 snake venoms, Broad et al. found in 1979 that some of the most potent venoms come from the Australian Elapidae family members Oxyuranus microlepidotus (O. microlepidotus; Inland tai